Conjugation of the monoclonal antibody 17-1A with the nitroacridine compound C921 with the poly-L-lysine as an intermediate agent

Transferrin and transferrin receptors play an important role in the transport of iron into the brain. To determine whether gallium enters the brain by the same mechanism, uptakes of 67Ga and 59Fe have been compared under controlled conditions. Rates of gallium penetration into brain (K(in)) were four times slower than those for 59Fe. K(in) for 67Ga when infused with citrate were 0.88 +/- 0.24 and 0.94 +/- 0.39 x 10(-3) ml g-1h-1 for cerebral hemisphere and cerebellum, respectively. When infused as the transferrin complex, 67Ga uptake into the brain was not different from that when infused with citrate. The presence of the anti-transferrin receptor antibody OX-26 significantly reduced uptake of 59Fe by 60% and 64% into cerebral hemisphere and cerebellum, respectively. By contrast, pretreatment of rats with OX-26 enhanced the uptake of 67Ga into brain, particularly when infused with citrate; mean increases in uptake of 67Ga were 120% and 144% for cerebral hemisphere and cerebellum, respectively. Purified 67Ga-transferrin was also taken up into both brain regions examined in the presence of OX-26. These results indicate that the transport of non-transferrin bound gallium is an important mechanism for gallium uptake into brain.